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Journal of Antimicrobial Chemotherapy (2001) 48, 501-506
© 2001 The British Society for Antimicrobial Chemotherapy

Ex vivo 12 h bactericidal activity of oral co-amoxiclav (1.125 g) against ß-lactamase-producing Haemophilus influenzae

Stéphane Bronner, Davide Pompei, Hassan Elkhaïli, Nathalie Dhoyen, Henri Monteil and François Jehl,*

Laboratoire d'Antibiologie Bactériennes, Institut de Bactériologie, Faculté de Médecine – Hôpitaux Universitaires de Strasbourg, 3 rue Koeberlé, F-67000 Strasbourg, France

The aim of the study was to evaluate the in vitro/ex vivo bactericidal activity of a new coamoxiclav single-dose sachet formulation (1 g amoxicillin + 0.125 g clavulanic acid) against a ß-lactamase-producing strain of Haemophilus influenzae. The evaluation covered the 12 h period after antibiotic administration. Serum specimens from the 12 healthy volunteers included in the pharmacokinetic study were pooled by time point and in equal volumes. Eight of 12 pharmacokinetic sampling time points were included in the study. At time points 0.5, 0.75, 1, 1.5, 2.5, 5, 8 and 12 h post-dosing, the kinetics of bactericidal activity were determined for each of the serial dilutions. Each specimen was serially diluted from 1:2 to 1:256. The index of surviving bacteria (ISB) was subsequently determined for each pharmacokinetic time point. For all the serum samples, bactericidal activity was fast (3–6 h), marked (3–6 log10 reduction in the initial inoculum) and sustained over the 12 h between-dosing interval. The results obtained also confirmed that the potency of the amoxicillin plus clavulanic acid combination was time dependent against the species under study and that the time interval over which the concentrations were greater than the MIC (t > MIC) was 100% for the strain under study. The data thus generated constitute an interesting prerequisite with a view to using co-amoxiclav 1.125 g in a bd oral regimen.

* Corresponding author. Tel: +33-3-9024-3790; Fax: +33-3-8825-1113; E-mail: francois.jehl{at}medecine.u-strasbg.fr


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